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Overview

Uniprot IDQ15054
Protein NameDNA polymerase delta subunit 3
Gene NamePOLD3
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
199 IMGMFASKAAAKTQE
227 NASAAGNKAPGKGNM
231 AGNKAPGKGNMMSNF
241 MMSNFFGKAAMNKFK
246 FGKAAMNKFKVNLDS
248 KAAMNKFKVNLDSEQ
274 TVSVTEPKLATPAGL
282 LATPAGLKKSSKKAE
283 ATPAGLKKSSKKAEP
292 SKKAEPVKVLQKEKK
445 EERKGPKKGTAALGK
452 KGTAALGKANRQVSI

Function

Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex (PubMed:17317665, PubMed:22801543, PubMed:24449906). As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA (PubMed:10219083, PubMed:10852724, PubMed:11595739, PubMed:16510448, PubMed:24035200). Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion (PubMed:19074196, PubMed:25628356, PubMed:27185888). Also involved in TLS, as a component of the tetrameric DNA polymerase zeta complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906)

Protein Sequence

10 MADQLYLENI 20 DEFVTDQNKI 30 VTYKWLSYTL 40 GVHVNQAKQM 50 LYDYVERKRK 60 ENSGAQLHVT 70 YLVSGSLIQN 80 GHSCHKVAVV 90 REDKLEAVKS 100 KLAVTASIHV 110 YSIQKAMLKD 120 SGPLFNTDYD 130 ILKSNLQNCS 140 KFSAIQCAAA 150 VPRAPAESSS 160 SSKKFEQSHL 170 HMSSETQANN 180 ELTTNGHGPP 190 ASKQVSQQPK 200 GIMGMFASKA 210 AAKTQETNKE 220 TKTEAKEVTN 230 ASAAGNKAPG 240 KGNMMSNFFG 250 KAAMNKFKVN 260 LDSEQAVKEE 270 KIVEQPTVSV 280 TEPKLATPAG 290 LKKSSKKAEP 300 VKVLQKEKKR 310 GKRVALSDDE 320 TKETENMRKK 330 RRRIKLPESD 340 SSEDEVFPDS 350 PGAYEAESPS 360 PPPPPSPPLE 370 PVPKTEPEPP 380 SVKSSSGENK 390 RKRKRVLKSK 400 TYLDGEGCIV 410 TEKVYESESC 420 TDSEEELNMK 430 TSSVHRPPAM 440 TVKKEPREER 450 KGPKKGTAAL 460 GKANRQVSIT GFFQRK

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0043625 delta DNA polymerase complex
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0016035 zeta DNA polymerase complex
Molecular Function GO:0030674 protein-macromolecule adaptor activity
Biological Process GO:0071897 DNA biosynthetic process
Biological Process GO:0006271 DNA strand elongation involved in DNA replication
Biological Process GO:0000731 DNA synthesis involved in DNA repair
Biological Process GO:1904161 DNA synthesis involved in UV-damage excision repair
Biological Process GO:0006261 DNA-templated DNA replication
Biological Process GO:0042276 error-prone translesion synthesis
Biological Process GO:0006298 mismatch repair
Biological Process GO:0006297 nucleotide-excision repair, DNA gap filling

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.

[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.